The crystal structure of the heme domain of endothelial nitric oxide synthase (eNOS) has been determined to 1.9 [unreadable]. NOS is the enzyme that converts L-arginine to nitric axide (NO) and L-citrulline. NO is a ptent biological signaling molecule in the immune, cardiovascular, and nervous systems. Both NO over and under production are associated with a number of pathological conditions so the design of isoform specific inhibitors is an important health related goal. NOS must be dimeric to function and since the heme domain is the critical target for drug design, we have focused on the structure of heme domain dimers. The structure to 1.9 [unreadable] contains a potent inhibitor, ehtylisothiourea, bound at the active site and at 2.3 [unreadable], the substrate-complex structure has been determined. The use of synchrotron radiation sources was absolutely essential for this work. Crystals diffract inhouse to about 3.0-3.5 [unreadable] but beyond 1.9 [unreadable] at synchrotron sources. In addition, extensive use of anomalous dispersion information was essential for obtaining an interpretable electron density map. An unexpected and novel feature in the structure is the identification of metal coordinated by pairs of symmetry related Cys residues at the dimer interface along the dyad axis of symmetry. Since several data sets were obtained at various wavelengths at CHESS and at other sources, it was possible to use anomalous difference Fouriers to identify the metal as zinc. The metal is crucial for forming the binding site for the essential cofactor, tetrhydrobiopterin, which in turn, is important for forming the substrate binding site. The identification of the new metal-S4 cluster has provided significant new insights into NOS structure and function which would not have been possible without synchrotron x-ray sources.